NDLI: Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes

Content Provider	PubMed Central
Author	Cordero, Dwight Ralph, Marcucio Hu, Diane William, Gaffield Tapadia, Minal Helms, Jill A.
Copyright Year	2004
Abstract	One of the most perplexing questions in clinical genetics is why patients with identical gene mutations oftentimes exhibit radically different clinical features. This inconsistency between genotype and phenotype is illustrated in the malformation spectrum of holoprosencephaly (HPE). Family members carrying identical mutations in sonic hedgehog (SHH) can exhibit a variety of facial features ranging from cyclopia to subtle midline asymmetries. Such intrafamilial variability may arise from environmental factors acting in conjunction with gene mutations that collectively reduce SHH activity below a critical threshold. We undertook a series of experiments to test the hypothesis that modifying the activity of the SHH signaling pathway at discrete periods of embryonic development could account for the phenotypic spectrum of HPE. Exposing avian embryos to cyclopamine during critical periods of craniofacial development recreated a continuum of HPE-related defects. The craniofacial malformations included hypotelorism, midfacial hypoplasia, and facial clefting and were not the result of excessive crest cell apoptosis. Rather, they resulted from molecular reprogramming of an organizing center whose activity controls outgrowth and patterning of the mid and upper face. Collectively, these data reveal one mechanism by which the variable expressivity of a disorder such as HPE can be produced through temporal disruption of a single molecular pathway.
Related Links	http://dx.doi.org/10.1172/jci200419596
Ending Page	494
Page Count	10
Starting Page	485
File Format	PDF
ISSN	00219738
Journal	Journal of Clinical Investigation
Issue Number	4
Volume Number	114
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2004-08-16
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog

The Mutational Spectrum of the Sonic Hedgehog Gene in Holoprosencephaly: SHH Mutations Cause a Significant Proportion of Autosomal Dominant Holoprosencephaly

Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly

White Matter Maturation in Holoprosencephaly

Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly

Novel Sonic Hedgehog Mutation in a Couple with VariableExpression of Holoprosencephaly

An Evolutionarily Conserved Network Mediates Development of the zona limitans intrathalamica, a Sonic Hedgehog-Secreting Caudal Forebrain Signaling Center

Ectopic sonic hedgehog signaling impairs telencephalic dorsal midline development: implication for human holoprosencephaly

Subcellular Localization of Patched and Smoothened, the Receptors for Sonic Hedgehog Signaling, in the Hippocampal Neuron

Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes

Similar Documents

Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog

The Mutational Spectrum of the Sonic Hedgehog Gene in Holoprosencephaly: SHH Mutations Cause a Significant Proportion of Autosomal Dominant Holoprosencephaly

Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly

White Matter Maturation in Holoprosencephaly

Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly

Novel Sonic Hedgehog Mutation in a Couple with VariableExpression of Holoprosencephaly

An Evolutionarily Conserved Network Mediates Development of the zona limitans intrathalamica, a Sonic Hedgehog-Secreting Caudal Forebrain Signaling Center

Ectopic sonic hedgehog signaling impairs telencephalic dorsal midline development: implication for human holoprosencephaly

Subcellular Localization of Patched and Smoothened, the Receptors for Sonic Hedgehog Signaling, in the Hippocampal Neuron

Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes