Abstract
Classically, trophic factors are considered as proteins which support neurons in their growth, survival, and differentiation. However, most neurotrophic factors also have important functions outside of the nervous system. Especially essential renal growth and differentiation regulators are glial cell line-derived neurotrophic factor (GDNF), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs). Here we discuss how trophic factor-induced signaling contributes to the control of ureteric bud (UB) branching morphogenesis and to maintenance and differentiation of nephrogenic mesenchyme in embryonic kidney. The review includes recent advances in trophic factor functions during the guidance of branching morphogenesis and self-renewal versus differentiation decisions, both of which dictate the control of kidney size and nephron number. Creative utilization of current information may help better recapitulate renal differentiation in vitro, but it is obvious that significantly more basic knowledge is needed for development of regeneration-based renal therapies.
Highlights
Known as neurotrophic factors, have important functions outside of the nervous system (Sariola, 2001; Vega et al, 2003; Prakash et al, 2010), especially transforming growth factor beta (TGFβ) superfamily members glial cell line-derived neurotrophic factor (GDNF), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs), which all together with their receptors and modulators are essential for normal renal development
We discuss in detail how trophic factors regulate the two major morphogenetic processes of kidney development: ureteric bud (UB) branching and nephron differentiation (Figure 1)
GDNF signaling via Ret and GFRα1 is critical for kidney development and underscores the relevance of reciprocal signaling between the UB and the MM in coordinating the balance of branching and nephrogenesis (Figure 4)
Summary
Reviewed by: Anna Julie Peired, Università degli Studi di Firenze, Italy Zubaida R. Trophic factors are considered as proteins which support neurons in their growth, survival, and differentiation. Most neurotrophic factors have important functions outside of the nervous system. Essential renal growth and differentiation regulators are glial cell line-derived neurotrophic factor (GDNF), bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs). We discuss how trophic factor-induced signaling contributes to the control of ureteric bud (UB) branching morphogenesis and to maintenance and differentiation of nephrogenic mesenchyme in embryonic kidney. The review includes recent advances in trophic factor functions during the guidance of branching morphogenesis and self-renewal versus differentiation decisions, both of which dictate the control of kidney size and nephron number.
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