Expression and function of Nkx6.3 in vertebrate hindbrain

Abstract

Homeodomain transcription factors serve important functions in organogenesis and tissue differentiation, particularly with respect to the positional identity of individual cells. The Nkx6 subfamily controls tissue differentiation in the developing central nervous system where they function as transcriptional repressor proteins. Recent work indicates that Nkx6.3 is expressed in hindbrain V2 interneurons that co-express Nkx6.1, suggesting the possibility of functional redundancy. Here, we report that Nkx6.3 expression is specific to Chx10 + V2a interneurons but not Gata3 + V2b interneurons of the hindbrain, and that Nkx6.3 expression appears to mark cells of the prospective medullary reticular formation. Molecular analysis of Nkx6.3 null embryonic mouse hindbrain did not reveal detectable defects in progenitor markers, motor neuron or V2 interneuron sub-types. Forced expression of Nkx6.3 and Nkx6.1 promote V2 interneuron differentiation in the developing chick hindbrain. These findings indicate Nkx6.3 function is dispensable for CNS development and lead to the proposal that absence of overt defects is due to functional compensation from a related homeodomain transcription factor. SectionNervous System Development; Regeneration and Aging

The obesity-associated gene Negr1 regulates aspects of energy balance in rat hypothalamic areas

“…Both deletions remove conserved, noncoding elements upstream of Negr1 , but the 8‐kb deletion removes the binding site for NKX6.1 (Willer et al 2009 ; Wheeler et al 2013 ). As NKX6.1 is a strong transcriptional repressor, this suggests that altered expression of Negr1 contributes to the regulation of BMI (Hafler et al 2008 ).…”

Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity

“…Although the 8kb deletion does not disrupt the coding sequence of any gene, it encompasses a single conserved transcription factor binding site for NKX6.1 18 ( Figure 4a and 4b ), which is known to be involved in neuronal development in the mid and hindbrain. We used Electrophoretic Mobility Shift Assay (EMSA) to confirm binding of NKX6.1 to its predicted binding site within the 8kb deletion ( Figure 4c ).…”

Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements

“…2c). For example, NKX6-3, a nervous system and stomach tissue developmental regulator 36,37 , exhibited cancer-specific expression via a new 5 0 exon skipping the canonical RefSeq NKX6.3 first exon (Fig. 2g, Supplementary Fig.…”