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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.07.007 Byline: Nicolas A.D. Christophorou, Michael Mende, Laura Lleras-Forero, Timothy Grocott, Andrea Streit Keywords: Cell adhesion; Cell shape; Chick; Eya1; Gata3; Invagination; Placode; Transcription factor Abstract: Crucial components of the vertebrate eye, ear and nose develop from discrete patches of surface epithelium, called placodes, which fold into spheroids and undergo complex morphogenesis. Little is known about how the changes in cell and tissue shapes are coordinated with the acquisition of cell fates. Here we explore whether these processes are regulated by common transcriptional mechanisms in the developing ear. After specification, inner ear precursors elongate to form the placode, which invaginates and is transformed into the complex structure of the adult ear. We show that the transcription factor Pax2 plays a key role in coordinating otic fate and placode morphogenesis, but appears to regulate each process independently. In the absence of Pax2, otic progenitors not only lose otic marker expression, but also fail to elongate due to the loss of apically localised N-cadherin and N-CAM. In the absence of either N-cadherin or N-CAM otic cells lose apical cell-cell contact and their epithelial shape. While misexpression of Pax2 leads to ectopic activation of both adhesion molecules, it is not sufficient to confer otic identity. These observations suggest that Pax2 controls cell shape independently from cell identity and thus acts as coordinator for these processes. Article History: Received 10 May 2010; Revised 2 July 2010; Accepted 6 July 2010

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.09.025 Byline: Nicolas A.D. Christophorou, Andrew P. Bailey, Sven Hanson, Andrea Streit Keywords: Chick; Eyes absent; Ear; Eye; Lens; Olfactory epithelium; Pax2; Pax3; Pax6; Sine oculis Abstract: In vertebrates, cranial placodes form crucial parts of the sensory nervous system in the head. All cranial placodes arise from a common territory, the preplacodal region, and are identified by the expression of Six1/4 and Eya1/2 genes, which control different aspects of sensory development in invertebrates as well as vertebrates. While So and Eya can induce ectopic eyes in Drosophila, the ability of their vertebrate homologues to induce placodes in non-placodal ectoderm has not been explored. Here we show that Six1 and Eya2 are involved in ectodermal patterning and cooperate to induce preplacodal gene expression, while repressing neural plate and neural crest fates. However, they are not sufficient to induce ectopic sensory placodes in future epidermis. Activation of Six1 target genes is required for expression of preplacodal genes, for normal placode morphology and for placode-specific Pax protein expression. These findings suggest that unlike in the fly where the Pax6 homologue Eyeless acts upstream of Six and Eya, the regulatory relationships between these genes are reversed in early vertebrate placode development. Author Affiliation: Department of Craniofacial Development, King's College London, Guy's Campus, Tower Wing Floor 27, London SE1 8RT, UK Article History: Received 12 June 2009; Revised 16 September 2009; Accepted 16 September 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.07.011 Byline: Donald Bell (a), Andrea Streit (a), Itziar Gorospe (b), Isabel Varela-Nieto (b), Berta Alsina (c), Fernando Giraldez (c) Keywords: Chick; Cochlear-vestibular ganglion; Ear development; Neuroblast; Neurogenesis; Otic vesicle; Proneural genes; Sensory precursors; Temporal specification Abstract: The otic placode generates the auditory and vestibular sense organs and their afferent neurons; however, how auditory and vestibular fates are specified is unknown. We have generated a fate map of the otic placode and show that precursors for vestibular and auditory cells are regionally segregated in the otic epithelium. The anterior-lateral portion of the otic placode generates vestibular neurons, whereas the posterior-medial region gives rise to auditory neurons. Precursors for vestibular and auditory sense organs show the same distribution. Thus, different regions of the otic placode correspond to particular sense organs and their innervating neurons. Neurons from contiguous domains rarely intermingle suggesting that the regional organisation of the otic placode dictates positional cues to otic neurons. But, in addition, vestibular and cochlear neurogenesis also follows a stereotyped temporal pattern. Precursors from the anterior-lateral otic placode delaminate earlier than those from its medial-posterior portion. The expression of the proneural genes NeuroM and NeuroD reflects the sequence of neuroblast formation and differentiation. Both genes are transiently expressed in vestibular and then in cochlear neuroblasts, while differentiated neurons express Islet1, Tuj1 and TrkC, but not NeuroM or NeuroD. Together, our results indicate that the position of precursors within the otic placode confers identity to sensory organs and to the corresponding otic neurons. In addition, positional information is integrated with temporal cues that coordinate neurogenesis and sensory differentiation. Author Affiliation: (a) Department of Craniofacial Development, King's College London, London SE1 9RT, UK (b) Instituto de Investigaciones Biomedicas 'Alberto Sols', (CSIC-UAM) CIBER-ER, c/Arturo Duperier 4, 28029 Madrid, Spain (c) CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona (UPF-PRBB), Dr. Aiguader 88, 08001, Barcelona, Spain Article History: Received 6 June 2008; Revised 9 July 2008; Accepted 9 July 2008

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.05.044 Byline: Sung-Hee Kil (a), Andrea Streit (b), Stephen T. Brown (a), Nidhi Agrawal (a), Andres Collazo (a), Maija H. Zile (c), Andrew K. Groves (a) Keywords: Otic placode; Hindbrain; Mesoderm; Induction; Rhombomeres; Vitamin A Abstract: The hindbrain and cranial paraxial mesoderm have been implicated in the induction and patterning of the inner ear, but the precise role of the two tissues in these processes is still not clear. We have addressed these questions using the vitamin-A-deficient (VAD) quail model, in which VAD embryos lack the posterior half of the hindbrain that normally lies next to the inner ear. Using a battery of molecular markers, we show that the anlagen of the inner ear, the otic placode, is induced in VAD embryos in the absence of the posterior hindbrain. By performing grafting and ablation experiments in chick embryos, we also show that cranial paraxial mesoderm which normally lies beneath the presumptive otic placode is necessary for otic placode induction and that paraxial mesoderm from other locations cannot induce the otic placode. Two members of the fibroblast growth factor family, FGF3 and FGF19, continue to be expressed in this mesodermal population in VAD embryos, and these may be responsible for otic placode induction in the absence of the posterior hindbrain. Although the posterior hindbrain is not required for otic placode induction in VAD embryos, the subsequent patterning of the inner ear is severely disrupted. Several regional markers of the inner ear, such as Pax2, EphA4, SOHo1 and Wnt3a, are incorrectly expressed in VAD otocysts, and the sensory patches and vestibulo-acoustic ganglia are either greatly reduced or absent. Exogenous application of retinoic acid prior to 30 h of development is able rescue the VAD phenotype. By performing such rescue experiments before and after 30 h of development, we show that the inner ear defects of VAD embryos correlate with the absence of the posterior hindbrain. These results show that induction and patterning of the inner ear are governed by separate developmental processes that can be experimentally uncoupled from each other. Author Affiliation: (a) Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 West 3rd Street, Los Angeles, CA 90057, USA (b) Department of Craniofacial Development, King's College London, Guy's Campus, St. Thomas Street, SE1 9RT, London (c) Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA Article History: Received 4 March 2005; Revised 25 May 2005; Accepted 25 May 2005

Sentry placodes are unique columnar epithelia with neurogenic potential that develop in the vertebrate head ectoderm next to the neural tube. They contribute to the paired sensory organs and the cranial sensory ganglia generating a wide variety of cell types ranging from lens fibres to sensory receptor cells and neurons. Although progress has been made in recent years to identify the molecular players that mediate placode specification, induction and patterning, the processes that initiate placode development are not well understood. One hypothesis suggests that all placode precursors arise from a common territory, the pre-placodal region, which is then subdivided to generate placodes of specific character. This model implies that their induction begins through molecular and cellular mechanisms common to all placodes. Embryological and molecular evidence suggests that placode induction is a multi-step process and that the molecular networks establishing the pre-placodal domain as well as the acquisition of placodal identity are surprisingly similar to those used in Drosophila to specify sensory structures. Keywords: Placode; Development; Nervous system

Cranial placodes are focal regions of columnar epithelium next to the neural tube that contribute to sensory ganglia and organs in the vertebrate head, including the olfactory epithelium and the crystalline lens of the eye. Using focal dye labelling within the presumptive placode domain, we show that lens and nasal precursors arise from a common territory surrounding the interior neural plate. They then segregate over time and converge to their final positions in discrete placodes by apparently directed movements. Since these events closely parallel the separation of eye and antennal primordia (containing olfactory sensory cells) from a common imaginal disc in Drosophila, we investigated whether the vertebrate homologues of Distalless (Dll) and Eyeless (Ey), which determine antennal and eye identity in the fly, playa role in segregation of lens and nasal precursors in the chick. Dlx5 and Pax6 are initially co-expressed by future lens and olfactory cells. As soon as presumptive lens cells acquire columnar morphology all Dlx family members are down-regulated in the placode, while Pax6 is lost in the olfactory region. Lens precursor cells that express ectopic Dlx5 never acquire lens-specific gene expression and are excluded from the lens placode to cluster in the head ectoderm. These results suggest that the loss of Dlx5 is required for cells to adopt a lens fate and that the balance of Pax6 and Dlx expression regulates cell sorting into appropriate placodal domains. Keywords: Chick; Distal-less; Dlx; Eye; Eyeless; Fate map; Nasal epithelium; Pax6; Placode; Sensory organ

The neural crest and sensory placodes arise from a region of the embryonic ectoderm that lies between the neural plate and future epidermis. While some of the signalling pathways that are involved in cell fate determination at the border of the neural plate have been characterised, it is still unclear how different signals are integrated. Transcription factors of the DLX gene family that may mediate such cell fate decisions are expressed at the border of the neural plate. Here, we demonstrate that DLX5 is involved in positioning this border by repressing neural properties and simultaneously by promoting the formation of border-like cells that express the neural fold markers MSX1 and BMP4 and the preplacodal region marker SIX4. However, DLX5 is not sufficient to impart epidermal character or to specify cell fates that arise at the border of the neural plate, like neural crest or fully formed sensory placodes, in a cell-autonomous manner. Additional signals are generated when mature neural plate and epidermis interact and these are required for neural crest formation. We propose that patterning of the embryonic ectoderm is a multistep process that sequentially subdivides the ectoderm into regions with defined cell fates. Keywords: Chick; Distal-less; DLX; Ectodermal patterning; Neural crest; Placode

During development, the vertebrate inner ear arises from the otic placode, a thickened portion of the ectoderm next to the hindbrain. Here, the first detailed fate maps of this region in the chick embryo are presented. At head process stages, placode precursors are scattered throughout a large region of the embryonic ectoderm, where they intermingle with future neural, neural crest, epidermal, and other placode cells. Within the next few hours, dramatic cell movements shift the future otic placode cells toward the midline and ultimately result in convergence to their final position next to rhombomeres 5-6. Individual cells and small cell groups undergo constant cell rearrangements and appear to sort out from nonotic cells. While the major portion of the otic placode is derived from the nonneural ectoderm, the neural folds also contribute cells to the placode at least until the four-somite stage. Comparison of these fate maps with gene expression patterns at equivalent stages reveals molecular heterogeneity of otic precursor cells in terms of their expression of d1x5, msx1, Six4, and ERNI. Although Pax2 expression coincides with the region where otic precursors are found from stage 8, not all Pax2-positive cells will ultimately contribute to the otic placode. Key Words: chicken; ear development; fate map; placode field.

Author(s): Andrea Streit [1]; Alyson J. Berliner [2]; Costis Papanayotou [1]; Andrés Sirulnik [1]; Claudio D. Stern [1, 2] During neural induction, the 'organizer' of the vertebrate embryo instructs neighbouring [...]

Data from the Institutional Population Component of the National Medical Expenditure Survey were used to provide national estimates of annual mental health service provision and use in nursing homes. In addition, the relationship between service provision and setting characteristics such as ownership, size, Medicaid certification, and chain status was examined. Although more than three quarters of residents with a mental disorder resided at a nursing home that provided counseling services, fewer than one fifth actually received any mental health services within the year. (Am J Public Health. 1994;84:284-287), It appears that less than 1/5 of nursing home residents who need mental health care actually receive mental health services. The 1987 National Medical Expenditure Survey estimated that 835,000 nursing home residents have a mental disorder and 75% of them live in a facility that offers mental health services. Approximately 60% of nursing homes offer either counseling or psychotherapy. However, 26.5% of these provide services through an outside contractor. Almost 83% of government facilities provide mental health services. Government facilities use psychiatrists or psychologists for mental health services more frequently than other facilities. For-profit facilities tend to use people with little advanced training to provide mental health care. Non-profit facilities tend to use psychiatrists, psychologist and social workers. Psychiatric social workers were the providers most commonly used by smaller facilities.