The ups and downs of holoprosencephaly: Dorsal versus ventral patterning forces

M. Fernandes, Jean M. Hebert

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Holoprosencephaly (HPE), characterized by incomplete separation of forebrain and facial components into left and right sides, is a common developmental defect in humans. It is caused by both genetic and environmental factors and its severity covers a wide spectrum of phenotypes. The genetic interactions underlying inherited forms of HPE are complex and poorly understood. Animal models, in particular mouse mutants, are providing a growing understanding of how the forebrain develops and how the cerebral hemispheres become split into left and right sides. These insights, along with the characterization to date of some of the genes involved in human HPE, suggest that two distinct mechanisms underlie the major classes of HPE, 'classic' and midline interhemispheric (MIH). Disruption either directly or indirectly of the ventralizing effect of sonic hedgehog signaling appears central to all or most forms of classic HPE, while disruption of the dorsalizing effect of bone morphogenetic protein signaling may be key to cases of MIH HPE.

Original languageEnglish (US)
Pages (from-to)413-423
Number of pages11
JournalClinical Genetics
Volume73
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Holoprosencephaly
Prosencephalon
Bone Morphogenetic Proteins
Hedgehogs
Cerebrum
Animal Models
Phenotype
Genes

Keywords

  • BMP
  • Cerebral hemispheres
  • Classic HPE
  • Dorsal-ventral patterning
  • MIH HPE
  • SHH
  • Telencephalon

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

The ups and downs of holoprosencephaly : Dorsal versus ventral patterning forces. / Fernandes, M.; Hebert, Jean M.

In: Clinical Genetics, Vol. 73, No. 5, 05.2008, p. 413-423.

Research output: Contribution to journalArticle

@article{caa1939d019641139e4e341e7d54b592,
title = "The ups and downs of holoprosencephaly: Dorsal versus ventral patterning forces",
abstract = "Holoprosencephaly (HPE), characterized by incomplete separation of forebrain and facial components into left and right sides, is a common developmental defect in humans. It is caused by both genetic and environmental factors and its severity covers a wide spectrum of phenotypes. The genetic interactions underlying inherited forms of HPE are complex and poorly understood. Animal models, in particular mouse mutants, are providing a growing understanding of how the forebrain develops and how the cerebral hemispheres become split into left and right sides. These insights, along with the characterization to date of some of the genes involved in human HPE, suggest that two distinct mechanisms underlie the major classes of HPE, 'classic' and midline interhemispheric (MIH). Disruption either directly or indirectly of the ventralizing effect of sonic hedgehog signaling appears central to all or most forms of classic HPE, while disruption of the dorsalizing effect of bone morphogenetic protein signaling may be key to cases of MIH HPE.",
keywords = "BMP, Cerebral hemispheres, Classic HPE, Dorsal-ventral patterning, MIH HPE, SHH, Telencephalon",
author = "M. Fernandes and Hebert, {Jean M.}",
year = "2008",
month = "5",
doi = "10.1111/j.1399-0004.2008.00994.x",
language = "English (US)",
volume = "73",
pages = "413--423",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - The ups and downs of holoprosencephaly

T2 - Dorsal versus ventral patterning forces

AU - Fernandes, M.

AU - Hebert, Jean M.

PY - 2008/5

Y1 - 2008/5

N2 - Holoprosencephaly (HPE), characterized by incomplete separation of forebrain and facial components into left and right sides, is a common developmental defect in humans. It is caused by both genetic and environmental factors and its severity covers a wide spectrum of phenotypes. The genetic interactions underlying inherited forms of HPE are complex and poorly understood. Animal models, in particular mouse mutants, are providing a growing understanding of how the forebrain develops and how the cerebral hemispheres become split into left and right sides. These insights, along with the characterization to date of some of the genes involved in human HPE, suggest that two distinct mechanisms underlie the major classes of HPE, 'classic' and midline interhemispheric (MIH). Disruption either directly or indirectly of the ventralizing effect of sonic hedgehog signaling appears central to all or most forms of classic HPE, while disruption of the dorsalizing effect of bone morphogenetic protein signaling may be key to cases of MIH HPE.

AB - Holoprosencephaly (HPE), characterized by incomplete separation of forebrain and facial components into left and right sides, is a common developmental defect in humans. It is caused by both genetic and environmental factors and its severity covers a wide spectrum of phenotypes. The genetic interactions underlying inherited forms of HPE are complex and poorly understood. Animal models, in particular mouse mutants, are providing a growing understanding of how the forebrain develops and how the cerebral hemispheres become split into left and right sides. These insights, along with the characterization to date of some of the genes involved in human HPE, suggest that two distinct mechanisms underlie the major classes of HPE, 'classic' and midline interhemispheric (MIH). Disruption either directly or indirectly of the ventralizing effect of sonic hedgehog signaling appears central to all or most forms of classic HPE, while disruption of the dorsalizing effect of bone morphogenetic protein signaling may be key to cases of MIH HPE.

KW - BMP

KW - Cerebral hemispheres

KW - Classic HPE

KW - Dorsal-ventral patterning

KW - MIH HPE

KW - SHH

KW - Telencephalon

UR - http://www.scopus.com/inward/record.url?scp=42049101496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42049101496&partnerID=8YFLogxK

U2 - 10.1111/j.1399-0004.2008.00994.x

DO - 10.1111/j.1399-0004.2008.00994.x

M3 - Article

C2 - 18394003

AN - SCOPUS:42049101496

VL - 73

SP - 413

EP - 423

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 5

ER -