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BackgroundThe early stages of ovarian follicle formation-beginning with the breakdown of germ cell cysts and continuing with the formation of primordial follicles and transition to primary and secondary follicles-are critical in determining reproductive life span and fertility. Previously, we discovered that global knockouts of germ cell-specific transcriptional co-regulators Sohlh1, Sohlh2, Lhx8, and Nobox, cause rapid oocyte loss and ovarian failure. Also factors such as Nobox and Sohlh1 are associated with human premature ovarian failure. In this study, we developed a conditional knockout of Lhx8 to study oocyte-specific pathways in postnatal folliculogenesis.ResultsThe conditional deficiency of Lhx8 in the oocytes of primordial follicles leads to massive primordial oocyte activation, in part, by indirectly interacting with the PI3K-AKT pathway, as shown by synergistic effects on FOXO3 nucleocytoplasmic translocation and rpS6 activation. However, LHX8 does not directly regulate members of the PI3K-AKT pathway; instead, we show that LHX8 represses Lin28a expression, a known regulator of mammalian metabolism and of the AKT/mTOR pathway. LHX8 can bind to the Lin28a promoter, and the depletion of Lin28a in Lhx8-deficient oocytes partially suppresses primordial oocyte activation. Moreover, unlike the PI3K-AKT pathway, LHX8 is critical beyond primordial follicle activation, and blocks the primary to secondary follicle transition.ConclusionsOur results indicate that the LHX8-LIN28A pathway is essential in the earliest stages of primordial follicle activation, and LHX8 is an important oocyte-specific transcription factor in the ovary for regulating postnatal folliculogenesis.

The enteric nervous system (ENS) consists of neurons and glial cells that differentiate from neural crest progenitors. During embryogenesis, development of the ENS is controlled by the interplay of neural crest cell-intrinsic factors and instructive cues from the surrounding gut mesenchyme. However, postnatal ENS development occurs in a different context, which is characterized by the presence of microbiota and an extensive immune system, suggesting an important role of these factors on enteric neural circuit formation and function. Initial reports confirm this idea while further studies in this area promise new insights into ENS physiology and pathophysiology., Introduction The enteric nervous system (ENS) encompasses the intrinsic neuroglial networks of the gut, which are organized into two layers of interconnected ganglia, the outer myenteric and the inner submucosal [...]

Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair (1). The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium (2). It has been thought for decades that the dental mesenchymal stem cells (3) giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue (4,5). Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique (6) with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth., Shortly after the dental placode is induced, nerves intimately associate with the developing tooth (7). To address whether glia-derived cells contribute to dental mesenchymal stem cells (MSCs) during tooth organogenesis, [...]

A highly complex network of intrinsic enteric neurons is required for the digestive and homeostatic functions of the gut. Nevertheless, the genetic and molecular mechanisms that regulate their assembly into [...]

The enteric nervous system (ENS) in mammals forms from neural crest cells during embryogenesis and early postnatal life. Nevertheless, multipotent progenitors of the ENS can be identified in the adult intestine using clonal cultures and in vivo transplantation assays. The identity of these neurogenic precursors in the adult gut and their relationship to the embryonic progenitors of the ENS are currently unknown. Using genetic fate mapping, we here demonstrate that mouse neural crest cells marked by SRY box-containing gene 10 (Sox10) generate the neuronal and glial lineages of enteric ganglia. Most neurons originated from progenitors residing in the gut during mid-gestation. Afterward, enteric neurogenesis was reduced, and it ceased between 1 and 3 months of postnatal life. Sox10-expressing cells present in the myenteric plexus of adult mice expressed glial markers, and we found no evidence that these cells participated in neurogenesis under steady-state conditions. However, they retained neurogenic potential, as they were capable of generating neurons with characteristics of enteric neurons in culture. Furthermore, enteric glia gave rise to neurons in vivo in response to chemical injury to the enteric ganglia. Our results indicate that despite the absence of constitutive neurogenesis in the adult gut, enteric glia maintain limited neurogenic potential, which can be activated by tissue dissociation or injury., Introduction Establishment of functional circuits in the nervous system depends on the precise spatiotemporal generation of interconnected neuronal subtypes. In the CNS, postmitotic neurons are generated from neural stem cells [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.07.001 Byline: Myrto Denaxa (a), Paul T. Sharpe (b), Vassilis Pachnis (a) Keywords: LIM homeodomain; Lhx6; Lhx7; Odontogenesis; Molars; Incisors Abstract: Genes encoding LIM homeodomain transcription factors are implicated in cell type specification and differentiation during embryogenesis. Two closely related members of this family, Lhx6 and Lhx7, are expressed in the ectomesenchyme of the maxillary and mandibular processes and have been suggested to control patterning of the first branchial arch (BA1) and odontogenesis. However, mice homozygous for single mutations either have no cranial defects (Lhx6) or show only cleft palate (Lhx7). To reveal the potential redundant activities of Lhx6 and Lhx7 in cranial morphogenesis, we generated mice with all combinations of wild-type and mutant alleles. Double homozygous mice have characteristic defects of the cranial skeleton and die shortly after birth, most likely because of cleft palate. In addition, Lhx6/7 deficient embryos lack molar teeth. The absence of molars in double mutants is not due to patterning defects of BA1 but results from failure of specification of the molar mesenchyme. Despite molar agenesis, Lhx6/7-deficient animals have normal incisors which, in the maxilla, are flanked by a supernumerary pair of incisor-like teeth. Our experiments demonstrate that the redundant activities of the LIM homeodomain proteins Lhx6 and Lhx7 are critical for craniofacial development and patterning of mammalian dentition. Author Affiliation: (a) Division of Molecular Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK (b) Department of Craniofacial Development, King's College, Guy's Hospital, London SE1 9RT, UK Article History: Received 21 January 2009; Revised 1 July 2009; Accepted 1 July 2009

A study examines gene interaction during the development of enteric nervous system. The role of endothelin is considered in the study.

The RET tyrosine kinase receptor isoforms and differential activities in mammalian embryogenesis are discussed. Targeted mutagenesis was used to generate mice that express RET9 or RET51. Some RET9 transgenes can rescue kidney agenesis in RET-deficient mice or can cause kidney hypodysplasia in wild-type animals. Mice without RET9 lack enteric ganglia from the colon. Human mutations of c-RET bring on Hirschsprung's disease.

The co-expression of Mox1 and Mox2 in the epithelial somites of mouse embryos continues in the sclerotome, although the dermomyotome only expresses Mox1. To study the role of Mox2 in the development of paraxial mosoderm, the first coding exon was disrupted by gene targeting in mouse embryonic stem (ES) stem cells, generating a null allele. Mox2 is not required for the migration of myogenic precursors into limb buds, but is necessary for normal appendicular muscle formation and normal regulation of myogenic genes.