Noggin producing, MyoD-positive cells are crucial for eye development

Abstract

A subpopulation of cells expresses MyoD mRNA and the cell surface G8 antigen in the epiblast prior to the onset of gastrulation. When an antibody to the G8 antigen was applied to epiblast, labeled cells were later found in the ocular primordial and muscle and non-muscle forming tissues of the eyes. In the lens, retina and periocular mesenchyme, G8-positive cells synthesized MyoD mRNA and the bone morphogenetic protein inhibitor Noggin. MyoD expressing cells were ablated in the epiblast by labeling them with the G8 MAb and lysing them with complement. Their ablation in the epiblast resulted in eye defects, including anopthalmia, micropthalmia, altered pigmentation and malformations of the lens and/or retina. The right eye was more severely affected than the left eye. The asymmetry of the eye defects in ablated embryos correlated with differences in the number of residual Noggin producing, MyoD-positive cells in ocular tissues. Exogenously supplied Noggin compensated for the ablated epiblast cells. This study demonstrates that MyoD expressing cells serve as a Noggin delivery system to regulate the morphogenesis of the lens and optic cup.

Unique precursors for the mesenchymal cells involved in injury response and fibrosis

“…In vivo, these cells are incorporated into somites where they function instead as cellsignaling centers that promote the myogenic differentiation of surrounding skeletal muscle progenitor cells through their release of Noggin, a bone morphogenetic protein inhibitor (16). G8 pos / MyoD pos cells also are incorporated into tissues that lack skeletal muscle (12,(17)(18)(19), including the embryonic lens (20), where our studies now suggest they play a principal role in wound repair and are a source of disease-causing myofibroblasts.…”

Role of Myo/Nog Cells in Neuroprotection: Evidence from the Light Damaged Retina

“…They were identified by their expression of mRNA for the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein (BMP) inhibitor Noggin and the cell surface protein recognized by the G8 monoclonal antibody (mAb)[1, 4–7]. During gastrulation, Myo/Nog cells become widely distributed in small numbers throughout the embryo [1, 3, 8]. Depletion of Myo/Nog cells in the blastocyst results in an inhibition of skeletal muscle differentiation, externalization of organs through the body wall and severe malformations of the central nervous system [1, 3, 8].…”

“…During gastrulation, Myo/Nog cells become widely distributed in small numbers throughout the embryo [1, 3, 8]. Depletion of Myo/Nog cells in the blastocyst results in an inhibition of skeletal muscle differentiation, externalization of organs through the body wall and severe malformations of the central nervous system [1, 3, 8]. …”

“…Our understanding of Myo/Nog cells was extended when it was discovered that Myo/Nog cells originating in the epiblast are critical for the development of the eye in chick [1, 8]. The first evidence of this role came when Myo/Nog cells tagged within the epiblast of the blastula were detected later in the developing eyecup and lens [1, 8].…”

“…The first evidence of this role came when Myo/Nog cells tagged within the epiblast of the blastula were detected later in the developing eyecup and lens [1, 8]. Depletion of Myo/Nog cells at this early embryonic period resulted in eye defects such as anophthalmia, microphthalmia, lens dysgenesis and abnormalities in the retina (e.g.…”