High impact information on Nkx2-3

• Expression of Nkx2.6 overlaps that of Nkx2.5 in the pharynx and heart and that of Nkx2.3 in the pharynx [1].
• Targeted disruption of the homeobox transcription factor Nkx2-3 in mice results in postnatal lethality and abnormal development of small intestine and spleen [2].
• The homeodomain transcription factor Nkx2-3 is expressed in gut mesenchyme and spleen of embryonic and adult mice [2].
• Taken together these observations indicate that Nkx2-3 is essential for normal development and functions of the small intestine and spleen [2].
• Spleens of Nkx2-3 mutants are generally smaller and contain drastically reduced numbers of lymphatic cells [2].

Biological context of Nkx2-3

• NK-2 class homeobox genes and pharyngeal/oral patterning: Nkx2-3 is required for salivary gland and tooth morphogenesis [3].
• These data suggest roles for Nkx2-3 during pharyngeal organogenesis, although the considerable potential for genetic redundancy within and outside of this gene family may mask earlier functions in organ specification [3].
• Interestingly, differentiated cell types of the intestinal epithelium are present in homozygous mutants, suggesting that Nkx2-3 is not required for their cell lineage allocation or migration-dependent differentiation [2].
• We report here that mice deficient in the homeobox gene Nkx2-3, expressed in developing visceral mesoderm, show a complex intestinal malabsorption phenotype and striking abnormalities of gut-associated lymphoid tissue and spleen suggestive of deranged leukocyte homing [4].
• Semiquantitative RT-PCR analysis and immunohistochemistry revealed down-regulation of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in endothelial cells in which Nkx2-3 is normally expressed [4].

Anatomical context of Nkx2-3

• Nkx2-3 was expressed in the pharyngeal floor and pouches, as well as in oral and branchial arch ectoderm [3].
• Examination of Nkx2-3 null mice revealed defects in maturation and cellular organisation of the sublingual glands [3].
• Villus formation in the small intestine appears considerably delayed in Nkx2-3(-)/- foetuses due to reduced proliferation of the epithelium, while massively increased growth of crypt cells ensues in surviving adult mutants [2].
• Architectural defects in the spleens of Nkx2-3-deficient mice are intrinsic and associated with defects in both B cell maturation and T cell-dependent immune responses [5].
• Furthermore, Nkx2-3(-/-) mice show an excess of conventional B cells in mesenteric lymph node and peritoneal cavity, whereas transitional B cells are rare in spleen but overrepresented in bone marrow [5].

Regulatory relationships of Nkx2-3

• Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera [4].

Other interactions of Nkx2-3

• Our data suggest a role for a homeodomain factor in establishing the developmental and positional cues in endothelia that regulate leukocyte homing through local control of cellular adhesion and identify MAdCAM-1 as a candidate target gene of Nkx2-3 [4].
• The murine homeobox genes Nkx2.3 and Nkx2.6 are located on chromosomes 19 and 14, respectively [6].
• Collectively, these data indicate a substantial role for Nkx2-3 in the correct association of lymphocytes and splenic stromal elements that is independent of chemokine expression [5].

References