The growth factors cascade and the dendrito-/synapto-genesis versus cell survival in adult hippocampal neurogenesis: The chicken or the egg

• We summarize the evidences suggesting a specific selection process for newborn neurons in adult hippocampal neurogenesis.
• The selection process is based on a late-onset apoptosis time window, unlike in development.
• The selection process is time-specific, and shows spatial regionalization, and cell compartmentalization.
• The reason for these features is because newborn neurons are incorporated to a already formed, functional circuit.
• The benefit is to use a selection criterion of activity/functionality of new neurons.

The decision between cellular survival and death is governed by a balance between proapoptotic versus antiapoptotic signaling cascades. Growth factors are key actors, playing two main roles both at developmental and adult stages: a supporting antiapoptotic role through diverse actions converging in the mitochondria, and a promoter role of cell maturation and plasticity through dendritogenesis and synaptogenesis, especially relevant for the adult hippocampal neurogenesis, a case of development during adulthood. Here, both parallel roles mutually feed forward each other (the success in avoiding apoptosis lets the cell to grow and differentiate, which in turn lets the cell to reach new targets and form new synapses accessing new sources of growth factors to support cell survival) in a circular cause and consequence, or a “the chicken or the egg” dilemma. While identifying the first case of this dilemma makes no sense, one possible outcome might have biological relevance: the decision between survival and death in the adult hippocampal neurogenesis is mainly concentrated at a specific time window, and recent data suggest some divergences between the survival and the maturational promoter effect of growth factors. This review summarizes these evidences suggesting how growth factors might contribute to the live-or-die decision of adult-born immature granule neurons through influencing the maturation of the young neuron by means of its connectivity into a mature functional circuit.