Biology Reference
In-Depth Information
kind of centralized ''generator'' of product, was to impose a level of control on the
amount of microtubule polymer and the numbers of microtubules available at
critical stages of neuronal development (Baas
1996
). We envisioned the activity of
the centrosome as being pulsatile, delivering bursts of new microtubules for
example just prior to dendritic differentiation or when needed to supply a rapid
increase in axonal growth.
We also noted, however, that it would be difficult to envision how the centrosome
could be called upon to generate and deploy bursts of new microtubules to be used
far down the length of the axon, for example, in the formation of a collateral branch.
On this basis, we posited that existing microtubules in the axon or the dendrites may
undergo localized severing events that could transform a single long microtubule
into a population of many short ones (Joshi and Baas
1993
). Each short microtubule
would inherit the lattice structure of the parent microtubule, and each short micro-
tubule would theoretically have the capability of assembling into a new long
microtubule. This would render the axon or dendrites, once formed, less dependent
upon or perhaps entirely independent of microtubule nucleation events at the cen-
trosome. Since positing these ideas, we have confirmed that sites of impending
branch formation do, indeed, display local severing of microtubules (Yu et al.
1994
),
and we have identified two different microtubule-severing proteins that participate
in axonal branch formation (Qiang et al.
2010
; Yu et al.
2008
). Of course, this begs
the question of whether microtubule severing could completely obviate the need for
an active centrosome, even within the cell body.
Over the past decade, most studies on the neuronal centrosome have focused on
neuronal migration, a phase of development some neurons undergo prior to axonal
and dendritic development. In migrating neurons, most of the microtubules are
attached to the centrosome, and this is important for pulling along the centrosome
(and accompanying nucleus and cell body) as the neuron journeys to its final
destination (Higginbotham and Gleeson
2007
). This raises the question of what
happens when the neuron ceases migration and sets forth to differentiate an axon
and dendritic arbor. Is there an upregulation of microtubule severing such that all
microtubules nucleated at the centrosome are now released? Does that centrosome
gradually lose its nucleating potency during development, or is the ability to
nucleate microtubules retained and used at key moments in development? In adult
neurons, is there a slow but steady flow of new microtubules from the centrosome,
or does the centrosome become quiescent in terms of manufacturing new micro-
tubules? These questions remain unanswered but there has recently been new
interest in whether or not the neuronal centrosome serves as a hub for microtubule-
based activity relevant to neuronal differentiation (de Anda et al.
2005
; Stiess et al.
2010
; Stiess and Bradke
2011
). Here, we review the older literature, summarize
exciting new findings, and ponder the unanswered questions.
