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Research has been conducted on the Hedgehog signaling pathway. Results suggest that Hedgehog signaling is important for organizing ventral cell pattern via the differential cell affinity control.

The authors review publications on the Hedgehog family of intercellular signaling proteins. The topics of interest include mediated by Hedgehog local interactions in the embryonic ectoderm of Drosophila, long-range signaling in Drosophila imaging discs, Hedgehog reception and control of Hh secretion and distribution.

The role of Nkx genes, transcription factors, in the ventral spinal cord as it relates to neural patterning is discussed in this perspective article. Three central questions can be seen from the general model. One deals with how the Sonic hedgehog (Shh) concentration gradient is generated, another with how the gradient is translated into distinct transcriptional responses, and the third with what the transcriptional regulators that lock in a particular neuronal or glial fate are. Evidence indicates cell type diversity in the dorsal and ventral central nervous system depends on the starting action of qualitatively distinct signals that act in a concentration-dependent way to set up autonomous subdomains of homeodomain protein activity along the D-V axis of the neural tube.

The essential function of Wnt-4 in mammary gland development is discussed. It is downstream of progesterone signaling. If the progesterone receptor is not present in mammary epithelium, ductal sidebranching does not take place. Ectopic expression of the photooncogene Wnt-1 overcomes this lack and its effects.

Results show that the transcriptional factor T (Brachyury) is involved in the Wnt signaling pathway and it modulates a balance between mesodermal and neural cell during gastrulation of mouse embryo.

Differentiation and proliferation of chondrocytes regulated by Indian hedgehog (Ihh) signaling, which is necessary for bone formation, is discussed. Analysis has been carried out in an Ihh null mutant, and a role for an Ihh/PTHrP feedback mechanism in control of chondrocyte maturation is indicated. Ihh signaling seems to be pivotal in coordinating several cellular processes essential for vertebrate skeleton morphogenesis.

A ventral-to-dorsal gradient determines the pituitary cell types producing different hormones. An experiment produces in vivo and in vitro proof of the stages involved in the pituitary cell development. The signals that herald the different stages are listed. These cells play a critical role in enabling the pituitary gland to maintain homeostasis.

The mouse gene Noggin appears to play a role in patterning of the neural tube and somite. Noggin encodes an antagonist of bone morphogenetic protein (BMP). Noggin does not appear to be required for neural induction, but plays an essential role in neural tube growth and development. Differentiation of the somite is also deficient in null mutants.

The generation and characterization of a genetically engineered mouse model in which all animals develop short latency malignant osteosarcoma is described. The model based on osteoblast-restricted deletion of p53 and pRb showed strong similarities between murine osteosarcoma and human osteosarcoma could be used to address the molecular genetics of osteosarcoma and develop novel therapeutic strategies.

The signaling of Sonic Hedgehog (Shh) morphogen is promoted by Gas 1 and Cdo proteins. The Shh signaling is crucial for the development of various parts of the central nervous system.

Hh signaling in NCC is crucial for normal patterning and growth of the face. Fox genes mediate the action of shh in facial development.

Research has been conducted on apical ectodermal ridge formation. The authors have attempted to demonstrate that Wnt3, expressed throughout the limb ectoderm, is important for normal limb development and critical in establishment apical ectodermal ridge.

Research has been conducted on Hip1, a Hedgehog-binding protein. The authors have investigated the developmental role of this protein via generation of Hip1 mutants, and have discused the interactions between Hedgehog and fibroblast growth factor signaling which controls early lung branching.

Presents a study that examined the role of hedgehog signaling in multiple aspects of embryonic development. Targeted disruption of Hip1 results in neonatal lethality with respiratory failure; Cause of the defective secondary branching in Hip1 mutant lungs; Model for Hip1's role in lung branching morphogenesis.

Facial abnormalities in human SHH mutants have implicated the Hedgehog (Hh) pathway in craniofacial development, but early defects in mouse Shh mutants have precluded the experimental analysis of this phenotype. Here, we removed Hh-responsiveness specifically in neural crest cells (NCCs), the multipotent cell type that gives rise to much of the skeleton and connective tissue of the head. In these mutants, many of the NCC-derived skeletal and nonskeletal components are missing, but the NCC-derived neuronal cell types are unaffected. Although the initial formation of branchial arches (BAs) is normal, expression of several Fox genes, specific targets of Hh signaling in cranial NCCs, is lost in the mutant. The spatially restricted expression of Fox genes suggests that they may play an important role in BA patterning. Removing Hh signaling in NCCs also leads to increased apoptosis and decreased cell proliferation in the BAs, which results in facial truncation that is evident by embryonic day 11.5 (E11.5). Together, our results demonstrate that Hh signaling in NCCs is essential for normal patterning and growth of the face. Further, our analysis of Shh-Fox gene regulatory interactions leads us to propose that Fox genes mediate the action of Shh in facial development. [ABSTRACT FROM AUTHOR]