UNSW Embryo- Development of the Nervous System Selected References- Sonic Hedgehog Back to Neural Notes selected refs / page 1 / page 2 Articles | Reviews | Books Links: Page 2 Page 1 PubMed Link About PubMed Note: A Selected List of References for Neural Development from PubMed March 1999. It was too difficult to keep neural development to one page so I have selected a few current Articles below and given a short description of the relevance to specific aspects of neural development. Internet access computers will be able to get abstract directly from PubMed (when available) by clicking Abstract below.

Articles Sonic Hedgehog Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP Cell 1993 Dec 31;75(7):1417-30 Abstract | Related Articles MH- This is the first paper that connected the drosophila gene to vertebrate neural development. The paper was followed up (in the same lab) with key experiments in the inductive role of shh and dorsalin for the neural tube. Cells expressing the receptor Patched, a multi-pass transmembrane protein, respond to shh. Shh is also proteolytically cleaved and modified (cholesterol addition), N- and C-terminals may have different signalling functions. Shh also patterns other tissues (see somites, lung, limb) Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA Nature 1996 Oct 3;383(6599):407-13 Abstract | Related Articles | OMIM- shh MH- Disruption of the shh gene leads to a phenotype in mice that is identical to the human disorder holoprosencephaly. This significantly shows the direct relationship between shh and neural patterning. (also disrupts other tissues, showing that shh is a signal that means different things to different tissues). A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities. Hahn H, Christiansen J, Wicking C, Zaphiropoulos PG, Chidambaram A, Gerrard B, Vorechovsky I, Bale AE, Toftgard R, Dean M, Wainwright B J Biol Chem 1996 May 24;271(21):12125-8 Abstract | Full Text | Related Articles MH- PTC, a vertebrate homolog of Drosophila gene- patched, receptor for shh Regulation of patched by sonic hedgehog in the developing neural tube. Marigo V, Tabin CJ Proc Natl Acad Sci U S A 1996 Sep 3;93(18):9346-51 Abstract | MH- PTC, a vertebrate homolog of Drosophila gene- patched Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Briscoe J, Sussel L, Serup P, Hartigan-O'Connor D, Jessell TM, Rubenstein JL, Ericson JNature 1999 Apr 15;398(6728):622-7 Abstract | MH- A recent paper describing the downstream genes responding to shh in the nervous system. Patched and Smoothened are shh receptors and the GLI family of transcription factors is also downstream. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Sasaki H, Nishizaki Y, Hui Cc, Nakafuku M, Kondoh H Development 1999;126(17):3915-3924 Abstract | Gli family zinc finger proteins are mediators of shh signaling in vertebrates. Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3. Dai P, Akimaru H, Tanaka Y, Maekawa T, Nakafuku M, Ishii SJ Biol Chem 1999 Mar 19;274(12):8143-52 A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Pierani A, Brenner-Morton S, Chiang C, Jessell TM Cell 1999 Jun 25;97(7):903-15 Abstract | MH- shh is not alone in patterning ventral spinal cord, with retinoids appearing to mediate this parallel pathway. Sonic hedgehog regulates the growth and patterning of the cerebellum. Dahmane N, Ruiz-i-Altaba A Development 1999 Jun;126(14):3089-100 Abstract | The molecular bases of brain development and CNS malignancies remain poorly understood. Here we show that Sonic hedgehog (Shh) signaling controls the development of the cerebellum at multiple levels. SHH is produced by Purkinje neurons, it is required for the proliferation of granule neuron precursors and it induces the differentiation of Bergmann glia. Blocking SHH function in vivo results in deficient granule neuron and Bergmann glia differentiation as well as in abnormal Purkinje neuron development. Thus, our findings provide a molecular model for the growth and patterning of the cerebellum by SHH through the coordination of the development of cortical cerebellar cell types. In addition, they provide a cellular context for medulloblastomas, childhood cancers of the cerebellum. Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum.Wallace VA Curr Biol 1999 Apr 22;9(8):445-8 Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Wechsler-Reya RJ, Scott MP Neuron 1999 Jan;22(1):103-14 We show that Sonic hedgehog (Shh), which is made by Purkinje cells, regulates the division of granule cell precursors (GCPs). Treatment of GCPs with Shh prevents differentiation and induces a potent, long-lasting proliferative response. Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors. Orentas DM, Hayes JE, Dyer KL, Miller RH Development 1999 Jun;126(11):2419-29 Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Marti E, Bumcrot DA, Takada R, McMahon AP Nature 1995 May 25;375(6529):322-5 The identity and patterning of ventral cell types in the vertebrate central nervous system depends on cell interactions. For example, induction of a specialized population of ventral midline cells, the floor plate, appears to require contact-mediated signalling by the underlying notochord, whereas diffusible signals from the notochord and floor plate can induce ventrolaterally positioned motor neurons. Sonic hedgehog (Shh), a vertebrate hedgehog-family member, is processed to generate two peptides (M(r) 19K and 26/27K) which are secreted by both of these organizing centres. Moreover, experiments in a variety of vertebrate embryos, and in neural explants in vitro, indicate that Shh can mediate floor-plate induction. Here we have applied recombinant Shh peptides to neural explants in serum-free conditions. High concentrations of Shh bound to a matrix induce floor plate and motor neurons, and addition of Shh to the medium leads to dose-dependent induction of motor neurons. All inducing activity resides in a highly conserved amino-terminal peptide (M(r) 19K). Moreover, antibodies that specifically recognize this peptide block induction of motor neurons by the notochord. We propose that Shh acts as a morphogen to induce distinct ventral cell types in the vertebrate central nervous system. Regionalization of Sonic hedgehog transcription along the anteroposterior axis of the mouse central nervous system is regulated by Hnf3-dependent and -independent mechanisms. Epstein DJ, McMahon AP, Joyner AL Development 1999 Jan;126(2):281-92 The axial midline mesoderm and the ventral midline of the neural tube, the floor plate, share the property of being a source of the secreted protein, Sonic hedgehog (Shh), which has the capacity to induce a variety of ventral cell types along the length of the mouse CNS. To gain insight into the mechanisms by which Shh transcription is initiated in these tissues, we set out to identify the cis-acting sequences regulating Shh gene expression. As an approach, we have tested genomic clones encompassing 35 kb of the Shh locus for their ability to direct a lacZ reporter gene to the temporally and spatially restricted confines of the Shh expression domains in transgenic mice. Three enhancers were identified that directed lacZ expression to distinct regions along the anteroposterior axis including the ventral midline of the spinal cord, hindbrain, rostral midbrain and caudal diencephalon, suggesting that multiple transcriptional regulators are required to initiate Shh gene expression within the CNS. In addition, regulatory sequences were also identified that directed reporter expression to the notochord, albeit, under limited circumstances. Sequence analysis of the genomic clones responsible for enhancer activity from a variety of organisms, including mouse, chicken and human, have identified highly conserved binding sites for the hepatocyte nuclear factor 3 (Hnf3) family of transcriptional regulators in some, but not all, of the enhancers. Moreover, the generation of mutations in the Hnf3-binding sites showed their requirement in certain, but not all, aspects of Shh reporter expression. Taken together, our results support the existence of Hnf3-dependent and -independent mechanisms in the direct activation of Shh transcription within the CNS and axial mesoderm. Reviews Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Goodrich LV, Johnson RL, Milenkovic L, McMahon JA, Scott MP Genes Dev 1996 Feb 1;10(3):301-12 Abstract |   Books