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Chronic up‐regulation of sonic hedgehog has little effect on postnatal craniofacial morphology of euploid and trisomic mice
Author(s) -
Singh Nandini,
Dutka Tara,
Reeves Roger H.,
Richtsmeier Joan T.
Publication year - 2016
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24361
Subject(s) - biology , sonic hedgehog , craniofacial , ploidy , morphology (biology) , hedgehog , anatomy , microbiology and biotechnology , genetics , signal transduction , gene
Background: In Ts65Dn, a mouse model of Down syndrome (DS), brain and craniofacial abnormalities that parallel those in people with DS are linked to an attenuated cellular response to sonic hedgehog (SHH) signaling. If a similarly reduced response to SHH occurs in all trisomic cells, then chronic up‐regulation of the pathway might have a positive effect on development in trisomic mice, resulting in amelioration of the craniofacial anomalies. Results: We crossed Ts65Dn with Ptch1 tm1Mps/+ mice and quantified the craniofacial morphology of Ts65Dn; Ptch +/− offspring to assess whether a chronic up‐regulation of the SHH pathway rescued DS‐related anomalies. Ts65Dn; Ptch1 +/− mice experience a chronic increase in SHH in SHH‐receptive cells due to haploinsufficiency of the pathway suppressor, Ptch1 . Chronic up‐regulation had minimal effect on craniofacial shape and did not correct facial abnormalities in Ts65Dn; Ptch +/− mice. We further compared effects of this chronic up‐regulation of SHH with acute pathway stimulation in mice treated on the day of birth with a SHH pathway agonist, SAG. We found that SHH affects facial morphology differently based on chronic vs. acute postnatal pathway up‐regulation. Conclusions: Our findings have implications for understanding the function of SHH in craniofacial development and for the potential use of SHH‐based agonists to treat DS‐related abnormalities. Developmental Dynamics 245:114–122, 2016 . © 2015 Wiley Periodicals, Inc.