Identification of CD44 as a cell surface marker for Müller glia precursor cells

Abstract

In the retina, both neurons and glia differentiate from a common progenitor population. CD44 cell surface antigen is a hyaluronic acid receptor expressed on mature Mü ller glial cells. We found that in the developing mouse retina, expression of CD44 was transiently observed at or around birth in a subpopulation of c-kit-positive retinal progenitor cells. During in vitro culture, purified CD44/c-kit-positive retinal progenitor cells exclusively differentiated into Mü ller glial cells and not into neurons, suggesting that CD44 marks a subpopulation of retinal progenitor cells that are fated to become glia. Overexpression of CD44 inhibited the extension of processes by the neural retina (Rich et al. 1995), and protecting neurons from damage (Garcia and Vecino 2003). Furthermore, they act as neural progenitors to regenerate neurons in response to acute damage, especially in lower vertebrates (Dyer and Cepko 2000;Ooto et al. 2004;Karl et al. 2008;Osakada et al. 2008). As in the brain, Müller glial cells are thought to differentiate along with neurons from a common progenitor in the retina (Cepko 1993 (Furukawa et al. 1997;Hojo et al. 2000). However, known markers of glial cell lineages -brain glial markers included -seem to expressed relatively late in glial differentiation. Therefore, identification of early as well as cell surface markers would greatly facilitate the elucidation of mechanisms governing neuron-glia cell fate decisions. CD44 is a widely expressed transmembrane glycoprotein and cell surface receptor for hyaluronic acid (HA) (Ponta et al. 2003). It is thought to mediate cell migration, adhesion, tissue differentiation, and cancer metastasis. Through its relatively long intracellular domain, HA-CD44 interactions stimulate Rac1 signaling, leading to cytoskeletal effects and cell migration in astrocytes (Ponta et al. 2003). Roles for HA and CD44 have been suggested in neural systems. HA is one of the major glycosaminoglycans in the extracellular matrix and plays important roles in morphogenesis, remodeling, and integrity of the CNS. In the uninjured CNS, expression of CD44 is restricted to astrocytes in the white matter. In the retina in an injured or degenerating condition, expression of CD44 has been observed (Kuhrt et al. 1997;Chaitin and Brun-Zinkernage 1998). Localization of CD44 to Müller cell apical microvilli has been shown by immunostaining in normal mature rodent retina (Chaitin et al. 1994;Chaitin and Brun-Zinkernage 1998). However, its expression in developing retina has not been reported before. We found that CD44 was transiently expressed in developing mouse retina at around the P1 stage. CD44-labeled retinal cells were fated to differentiate into Müller glial cells, suggesting that CD44 labels the subset of retinal progenitor cells that becomes Müller glial cells. Experimental proceduresMice and reagents Enhanced green fluorescent protein (EGFP) transgenic mice, which express the EGFP gene ubiquitously via the Cytomegalovirus early enhancer element and chicken beta-actin promoter, w...

Coating nanocarriers with hyaluronic acid facilitates intravitreal drug delivery for retinal gene therapy

“…[13]. HA might be an interesting molecule for ocular delivery as well since it is a major constituent of the vitreous humour [20], is found throughout the retina [21] and many retinal cell types have been shown to express CD44-receptors on their surface [22,23]. vitro with minimal cytotoxicity, owing to the repetitive disulfide linkages in the main poly(amido amine) backbone [9,24].…”

Prion Replication Elicits Cytopathic Changes in Differentiated Neurosphere Cultures

“…5A). In addition, we observed that cells positive for CD44, which has recently been associated with astrocyte precursors in the developing central nervous system (49)(50)(51), displayed morphological abnormalities in infected dNP20 cultures (data not shown). Considering our present data together with previous findings, we propose that prions may induce cytopathic changes in astrocyte lineage cells, which may not differentiate into fully mature astrocytes.…”

CD44 Expression in Microglia of the Retina and Cerebellum of Developing and Adult Chicken

“…However, some studies have showed CD44 expression in astrocytes during development and adult; astrocyte precursor cells in developing chick [4,5], mice and rat [6,7,22], Müller glial cells in mice retina [9]. In some human disease, CD44 expression was reported in astrocyte-restricted precursor cells or reactive astrocytes [3,23].…”

“…Besides the CNS, CD44 expression was also reported in the retina. In mature mice retina, CD44 expressed on Müller glial cells [9]. In developing retina of the mice, CD44 was not detected at E15, transiently expressed in cells at around P1 day which will differentiate into Müller glial cells, and after P15 day it was increased to adult level [9].…”