Donovan, APA;
Yu, T;
Ellegood, J;
Riegman, KLH;
de Geus, C;
van Ravenswaaij-Arts, C;
Fernandes, C;
... Basson, MA; + view all
(2017)
Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of Chd7 from the Embryonic Mid-Hindbrain Region.
Frontiers in Neuroanatomy
, 11
, Article 86. 10.3389/fnana.2017.00086.
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Abstract
Reduced fibroblast growth factor (FGF) signaling from the mid-hindbrain or isthmus organizer (IsO) during early embryonic development results in hypoplasia of the midbrain and cerebellar vermis. We previously reported evidence for reduced Fgf8 expression and FGF signaling in the mid-hindbrain region of embryos heterozygous for Chd7, the gene mutated in CHARGE (Coloboma, Heart defects, choanal Atresia, Retarded growth and development, Genitourinary anomalies and Ear defects) syndrome. However, Chd7+/− animals only exhibit mild cerebellar vermis anomalies. As homozygous deletion of Chd7 is embryonic lethal, we conditionally deleted Chd7 from the early embryonic mid-hindbrain region to identify the function of CHD7 in mid-hindbrain development. Using a combination of high resolution structural MRI and histology, we report striking midbrain and cerebellar vermis hypoplasia in the homozygous conditional mutants. We show that cerebellar vermis hypoplasia is associated with reduced embryonic Fgf8 expression and an expanded roof plate in rhombomere 1 (r1). These findings identify an essential role for Chd7 in regulating mid-hindbrain development via Fgf8.
| Type: | Article |
|---|---|
| Title: | Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of Chd7 from the Embryonic Mid-Hindbrain Region |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnana.2017.00086 |
| Publisher version: | http://doi.org/10.3389/fnana.2017.00086 |
| Language: | English |
| Additional information: | Copyright © 2017 Donovan, Yu, Ellegood, Riegman, de Geus, van Ravenswaaij-Arts, Fernandes, Lerch and Basson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | CHD7, mid-hindbrain, cerebellum, vermis, hypoplasia |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10041171 |
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