| First Author | Kitazawa T | Year | 2022 |
| Journal | J Dev Biol | Volume | 10 |
| Issue | 1 | PubMed ID | 35225962 |
| Mgi Jnum | J:320009 | Mgi Id | MGI:6867213 |
| Doi | 10.3390/jdb10010009 | Citation | Kitazawa T, et al. (2022) Different Ectopic Hoxa2 Expression Levels in Mouse Cranial Neural Crest Cells Result in Distinct Craniofacial Anomalies and Homeotic Phenotypes. J Dev Biol 10 |
| abstractText | Providing appropriate positional identity and patterning information to distinct rostro-caudal subpopulations of cranial neural crest cells (CNCCs) is central to vertebrate craniofacial morphogenesis. Hox genes are not expressed in frontonasal and ï¬rst pharyngeal arch (PA1) CNCCs, whereas a single Hox gene, Hoxa2, is necessary to provide patterning information to second pha-ryngeal arch (PA2) CNCCs. In frog, chick and mouse embryos, ectopic expression of Hoxa2 in Hox-negative CNCCs induced hypoplastic phenotypes of CNCC derivatives of variable severity, associated or not with homeotic transformation of a subset of PA1 structures into a PA2-like identity. Whether these different morphological outcomes are directly related to distinct Hoxa2 overexpression levels is unknown. To address this issue, we selectively induced Hoxa2 overexpression in mouse CNCCs, using a panel of mouse lines expressing different Hoxa2 ectopic expression levels, including a newly generated Hoxa2 knocked-in mouse line. While ectopic Hoxa2 expression at only 60% of its physiological levels was sufï¬cient for pinna duplication, ectopic Hoxa2 expression at 100% of its normal level was required for complete homeotic repatterning of a subset of PA1 skeletal ele-ments into a duplicated set of PA2-like elements. On the other hand, ectopic Hoxa2 overexpression at non-physiological levels (200% of normal levels) led to an almost complete loss of craniofacial skeletal structures. Moreover, ectopic Hoxa5 overexpression in CNCCs, while also resulting in severe craniofacial defects, did not induce homeotic changes of PA1-derived CNCCs, indicating Hoxa2 speciï¬city in repatterning a subset of Hox-negative CNCCs. These results reconcile some discrepan-cies in previously published experiments and indicate that distinct subpopulations of CNCCs are differentially sensitive to ectopic levels of Hox expression. |
