Contributions by members of the TGFbeta superfamily to lens development

Crim1KST264/KST264 mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems

“…While complicated by not being a null mutation, the complex phenotype observed in the Crim1 KST264/KST264 mice is not easily explained by disruption to a single known BMP or TGF-␤, although some aspects are similar to those observed in disruption to members of this superfamily. The reduced lens and microphthalmia observed in Crim1 KST264/KST264 mice are perhaps most similar to those in BMP7 null mice (Dudley et al, 1995;Luo et al, 1995;Karsenty et al, 1996;Jena et al, 1997) and a conditional knockout of BMPR-1A (Beebe et al, 2004). Similarly, BMP7 null mice display dysplastic kidneys (Dudley et al, 1995;Luo et al, 1995;Karsenty et al, 1996;Jena et al, 1997) as do Crim1 KST264/KST264 , albeit less severely.…”

TGFβ pathobiology in the eye

“…The nuclei of elongating lens fiber cells are positive for phospho-Smad1, an indicator of signaling through BMP receptors. 50 These data indicate that BMPs participate in the differentiation of lens fiber cells, along with at least one additional, and still unknown factor. In mature lens fibers, the nuclei are degraded by apoptosis and this apoptotic process is also modulated by Smad signals.…”

“…In mature lens fibers, the nuclei are degraded by apoptosis and this apoptotic process is also modulated by Smad signals. 50 In addition to BMPs, TGFbs are also involved in lens fiber differentiation. 50 Overexpression of dominant-negative forms of either type I or type II TGFb receptors in the lens fibers of transgenic mice using mouse aA-crystallin promoter results in the development of pronounced bilateral nuclear cataracts.…”

“…50 In addition to BMPs, TGFbs are also involved in lens fiber differentiation. 50 Overexpression of dominant-negative forms of either type I or type II TGFb receptors in the lens fibers of transgenic mice using mouse aA-crystallin promoter results in the development of pronounced bilateral nuclear cataracts. The phenotype was characterized by attenuated lens fiber elongation in the cortex and disruption of fiber differentiation, culminating in fiber cell apoptosis and degeneration in the lens nucleus.…”

Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens

“…Finally, some of these specific DNAbinding transcription factors have to be connected with specific signal transduction pathways (FGF, TGFβ and BMP) that control lens development and lens fiber cell differentiation ( Fig. 2A) and described in this issue (see Beebe et al, 2004;Chen et al, 2004).…”