Bcl11b/Ctip2 is required for development of lingual papillae in mice

Abstract

Molecular mechanisms underlying the development and morphogenesis of oral epithelia, comprising the gustatory and nongustatory epithelium, remain unclear. Here, we show that Bcl11b, a zinc finger transcription factor, plays an important role in the development of lingual papillae, especially filiform papillae. In both gustatory and nongustatory epithelium, Bcl11b was expressed in keratin 14-positive epithelial basal cells, which differentiate into keratinocytes and/or taste cells. Loss of Bcl11b function resulted in abnormal morphology of the gustatory papillae: flattened fungiform papillae, shorter trench wall in the foliate and circumvallate papillae, and ectopic invagination in more than half of circumvallate papillae. However, Bcl11b loss caused no effect on differentiation of taste receptor cells. In nongustatory epithelium, the impact of Bcl11b deficiency was much more striking, resulting in a smooth surface on the tongue tip and hypoplastic filiform papillae in the dorsal lingual epithelium. Immunohistochemical analyses revealed that a keratinocyte differentiation marker, Tchh expression was severely decreased in the Bcl11b(-/-) filiform papillae. In addition, expression of Pax9, required for morphogenesis of filiform papillae and its downstream target genes, hard keratins, almost disappeared in the tongue tip and was decreased in the dorsal tongue of Bcl11b(-/-) mice. Gene expression analyses demonstrated a delayed onset of expression of epithelial differentiation complex genes, which disturbed barrier formation in the mutant tongue. These results indicate that Bcl11b regulates the differentiation of keratinocytes in the tongue and identify Bcl11b as an essential factor for the lingual papilla morphogenesis.

SOX2 regulates homeostasis of taste bud cells and lingual epithelial cells in posterior tongue

“…Lineage tracing of Sox2-deleted stem/progenitor cells revealed continuous generation of epithelial cells, and the morphology of the FiP appeared normal after the Sox2 deletion, even after three months (Fig 7A). In agreement, Krt35 and Krt84 (hard keratin genes expressed in the differentiated keratinocytes) and Pax9 and BCL11B (transcription factors required for keratinocyte differentiation) [35,36] appeared normal in intensity and distribution ( Figs 7C and S4A). Quantitative RT-PCR also showed no significant difference of Pax9, Bcl11b, or Krt35 expression by Sox2 deletion, although Krt84 mRNA expression was significantly decreased (Figs 7D and S4B).…”

Intrinsic Disorder of the BAF Complex: Roles in Chromatin Remodeling and Disease Development

“…BCL11B is involved in the processes of the development, differentiation, and survival of T-lymphocytes in the thymus, and serves as a regulator of IL2 promoter enhancing IL2 expression in activated CD4 + T-lymphocytes [197]. It participates in the differentiation of variable areas of the central nervous system, such as the hippocampal neurons and the medium spiny neurons of the striatum [198], acts as a regulator of the responsiveness of hematopoietic stem cells to chemotactic signals, and modulates expression of the CCR7 and CCR9 receptors directing the movement of progenitor cells from the bone marrow to the thymus [199]. BCL11B was also found to be highly expressed in the cells of the immune system and the skin epithelial cells, and is required for skin morphogenesis [198].…”

“…It participates in the differentiation of variable areas of the central nervous system, such as the hippocampal neurons and the medium spiny neurons of the striatum [198], acts as a regulator of the responsiveness of hematopoietic stem cells to chemotactic signals, and modulates expression of the CCR7 and CCR9 receptors directing the movement of progenitor cells from the bone marrow to the thymus [199]. BCL11B was also found to be highly expressed in the cells of the immune system and the skin epithelial cells, and is required for skin morphogenesis [198]. It participates in the regulation of terminal differentiation of keratinocytes and the development of the papillary structure of the lingual epithelium [198].…”

“…BCL11B was also found to be highly expressed in the cells of the immune system and the skin epithelial cells, and is required for skin morphogenesis [198]. It participates in the regulation of terminal differentiation of keratinocytes and the development of the papillary structure of the lingual epithelium [198].…”

Bcl11b—A Critical Neurodevelopmental Transcription Factor—Roles in Health and Disease

“…Similar to maintenance of mammary epithelium Bcl11b has an important role in epidermal stem cell maintenance and integrity as well as sphingolipid biosynthesis (Ganguli-Indra et al, 2009; Wang et al, 2012a; Bollag, 2013; Inoue et al, 2016). Bcl11b functionally directs mammalian odontogenesis and is crucial for the morphogenesis of lingual papilla and differentiation of oral epithelium (Kyrylkova et al, 2012; Nishiguchi et al, 2016). …”