Expression of Islet1 in thyroid development related to budding, migration, and fusion of primordia

Abstract

The LIM homeodomain transcription factor Isl1 was investigated in mouse thyroid organogenesis. All progenitor cells of the midline thyroid diverticulum and lateral primordia (ultimobranchial bodies) expressed Isl1. This pattern persisted until the growing anlagen fused at embryonic day (E) 13.5. In Isl1 null mutants thyroid progenitors expressing Nkx2.1 and Pax8 were readily specified in the anterior endoderm but the size of the thyroid rudiment was reduced. In late development, only immature C-cells expressed Isl1. In the adult gland the number of Isl1؉ cells was small compared with cells expressing calcitonin. Analysis of microarray profiles indicated a higher level of Isl1 expression in medullary thyroid carcinomas than in tumors derived from follicular cells. Together, these findings suggest that Isl1 may be a novel regulator of thyroid development before terminal differentiation of the endocrine cell types. Isl1 is an embryonic C-cell precursor marker that may be relevant also in cancer developed from the mature C-cell. Developmental Dynamics 237:3820 -3829, 2008.

Morphogenesis of the thyroid gland

“…This possibility needs to be formally proven, ultimately by genetic fate mapping of endoderm progenitors. However, in support of this novel concept Isl, which marks M a n u s c r i p t 47 definitive endoderm but not NCC was recently found to be expressed first in the UB epithelium and later on only by C-cell precursors and C-cells (Westerlund et al, 2008). Notably, the signaling pathways that could impose neuroendocrine features on cells of supposedly endodermal derivation are beginning to be characterized.…”

“…The mutant is embryonic lethal at E10.5 due to failure of the cardiovascular system to further develop. A possible additional role of Isl1 in thyroid organogenesis, as suggested by persisting expression of Isl1 in progenitor cells during migration of primordia (Westerlund et al, 2008), is presently not possible to appreciate.…”

“…Another example of a developmentally important transcription factor expressed in both thyroid and heart progenitor cells is Isl1 (Westerlund et al, 2008). Heart development is severely disturbed in Isl1 deficient mouse embryos involving defective reciprocal signaling between the cardiac mesoderm and the pharyngeal endoderm (Cai et al, 2003).…”

“…Heart development is severely disturbed in Isl1 deficient mouse embryos involving defective reciprocal signaling between the cardiac mesoderm and the pharyngeal endoderm (Cai et al, 2003). The thyroid bud is smaller in Isl1 null mutant embryos (Westerlund et al, 2008). This may be the result of decreased cell survival in the pharyngeal endoderm that is normally supported by Isl (Cai et al, 2003).…”

“…Notably, the signaling pathways that could impose neuroendocrine features on cells of supposedly endodermal derivation are beginning to be characterized. The identification of the transcription factor Mash1 (Kameda et al, 2007b) and Isl1 (Westerlund et al, 2008) as potential regulators of C-cell development signifies initial steps in this direction.…”