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A Highly Conserved Shh Enhancer Coordinates Hypothalamic and Craniofacial Development
- Source :
- Frontiers in Cell and Developmental Biology, Vol 9 (2021), Frontiers in Cell and Developmental Biology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Enhancers that are conserved deep in evolutionary time regulate characteristics held in common across taxonomic classes. Here, deletion of the highly conservedShhenhancer SBE2 (Shhbrain enhancer 2) in mouse markedly reducedShhexpression within the embryonic brain specifically in the rostral diencephalon; however, no abnormal anatomical phenotype was observed. Secondary enhancer activity was subsequently identified which likely mediates low levels of expression. In contrast, when crossing the SBE2 deletion with theShhnull allele, brain and craniofacial development were disrupted; thus, linking SBE2 regulatedShhexpression to multiple defects and further enabling the study of the effects of differing levels ofShhon embryogenesis. Development of the hypothalamus, derived from the rostral diencephalon, was disrupted along both the anterior-posterior (AP) and the dorsal-ventral (DV) axes. Expression of DV patterning genes and subsequent neuronal population induction were particularly sensitive toShhexpression levels, demonstrating a novel morphogenic context forShh. The role of SBE2, which is highlighted by DV gene expression, is to step-up expression ofShhabove the minimal activity of the second enhancer, ensuring the necessary levels ofShhin a regional-specific manner. We also show that lowShhlevels in the diencephalon disrupted neighbouring craniofacial development, including mediolateral patterning of the bones along the cranial floor and viscerocranium. Thus, SBE2 contributes to hypothalamic morphogenesis and ensures there is coordination with the formation of the adjacent midline cranial bones that subsequently protect the neural tissue.
- Subjects :
- 0301 basic medicine
animal structures
Morphogenesis
Context (language use)
Biology
Shh
craniofacial formation
Cell and Developmental Biology
03 medical and health sciences
Diencephalon
hypothalamic development
0302 clinical medicine
Gene expression
Enhancer
lcsh:QH301-705.5
Original Research
Embryogenesis
Cell Biology
Phenotype
Null allele
Cell biology
030104 developmental biology
lcsh:Biology (General)
embryonic development
embryonic structures
enhancer
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 2296634X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Cell and Developmental Biology
- Accession number :
- edsair.doi.dedup.....7d10087ee32257c4f8c65a83cab37c60
- Full Text :
- https://doi.org/10.3389/fcell.2021.595744