English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Cleft palate is a common birth defect in humans. Therefore, understanding the molecular genetics of palate development is important from both scientific and medical perspectives.  Lhx6  and  Lhx8  encode LIM homeodomain transcription factors, and inactivation of both genes in mice resulted in profound craniofacial defects including cleft secondary palate. The initial outgrowth of the palate was severely impaired in the mutant embryos, due to decreased cell proliferation. Through genome-wide transcriptional profiling, we discovered that  p57 Kip2   ( Cdkn1c ), encoding a cell cycle inhibitor, was up-regulated in the prospective palate of  Lhx6 −/− ;Lhx8 −/−   mutants.  p57 Kip2   has been linked to Beckwith–Wiedemann syndrome and IMAGe syndrome in humans, which are developmental disorders with increased incidents of palate defects among the patients. To determine the molecular mechanism underlying the regulation of  p57 Kip2   by the  Lhx  genes, we combined chromatin immunoprecipitation,  in silico  search for transcription factor-binding motifs, and  in vitro  reporter assays with putative cis-regulatory elements. The results of these experiments indicated that LHX6 and LHX8 regulated  p57 Kip2   via both direct and indirect mechanisms, with the latter mediated by Forkhead box (FOX) family transcription factors. Together, our findings uncovered a novel connection between the initiation of palate development and a cell cycle inhibitor via LHX. We propose a model in which  Lhx6  and  Lhx8  negatively regulate  p57 Kip2   expression in the prospective palate area to allow adequate levels of cell proliferation and thereby promote normal palate development. This is the first report elucidating a molecular genetic pathway downstream of  Lhx  in palate development.

Lhx6 and Lhx8 promote palate development through negative regulation of a cell cycle inhibitor gene, p57 Kip2