All pieces are now assembled: we know a little bit about the modular nature of brain development, we know a little bit about heterochrony, and we know a little bit about correlated evolution. We can now try to lay down the theory of “late equals large”.

According to Finlay and Darlington ¹, the fundamental force which drives change in brain size, as well as the size of individual regions, is the sheer number of neurons which compose it, as well as the amount of connections the neuron must make. The diameters of some cells and the volume of their connections vary in an orderly fashion with brain size ^{2 3}. More interestingly, the number of neurons can be studied in a more straightforward manner, because this trait seems to depend on development.
The number of cells in a structure can increase either via change in the rate at which precursor cells are produced or in the length of time over which they are produced. We have investigated both of these possibilities, beginning with changes in duration, measured by determining the peak of “neuronal birthdays” in the structure or cell group under consideration. Early in the development of the nervous system, each precursor cell located in the ventricular zone divides and produces two daughter cells, each of which can further divide. These symmetric divisions produce precursors whose numbers increase at an exponential rate. The birthday of a neuron is said to occur when a precursor cell divides “asymmetrically” and the resulting cell migrates from its initial position in the ventricular zone of the neural tube to a distant position, where it differentiates into a neuron. The time from conception to the peak of neuronal birthdays in a structure is a measure of the duration of cytogenesis for that particular structure. The longer peak birthday is delayed, the more precursor cells can be produced, which will increase the size of the particular structure. Therefore, if a single structure in the brain were to gain more cells by this method, its peak of neurogenesis would be delayed ⁴
By analyzing schedules of neurogenesis and brain sizes (or the size of individual regions) across diverse mammalian species, Finlay and Darlington demonstrated a simple relationship between how structures increase in relation to brain size (that is, the allometric growth curves for region size and brain size) and the order of neurogenesis: structures whose neurons are born late get disproportionately larger as absolute brain size increases. Consider this figure:

Here, the peaks of neurogenesis for three structures (A, B, and C) were transformed from the schedule of the mouse to the schedule of a monkey; a nonlinear rearrangement of total neural population for the final structures A, B and C can be appreciated. We can also notice, when we compare mice and monkeys, that the neural precursors for structure C are in production for about 80 days in the monkey, versus 18 in the mouse. In this case, both start and end parameters for development (a and b, that we have met in the last post) are changed, but Δb seems to be higher than Δa. As we saw in the general theoretical frame for heterochronic changes in development, changes in Δb should entice peramorphosis, which is somewhat counterbalanced by the changes in Δa. Marsupials, on the other hand, have the same event order, producing brains of different sizes, but the pace of neuronal production (the rate ky that we met in the last post) is slowed; as predicted by the theoretical model of heterochrony ⁵, this should result in pedomorphosis (reduction in neuronal population sizes), but this does not seem to be the case in marsupials – at least not for trait B. This could happen because, in these species, trait B is relatively non-correlated with brain size or epigenetic events.
This is an elegant theory for one mechanism that could contribute to brain evolution, and is in the modern tradition of evolutionary developmental biology (evo-devo) by incorporating development in the scheme. However, the theory still waits further developments (no pun intended); it has been pointed that resorting solely on development to explain evolutionary changes (a la the latter Stephen Jay Gould) underscores the role of microevolutionary mechanisms (random genetic drift, mutation, the various types of selection) in shaping morphological evolution. The late-equals-large rule is an interesting explanation of the law-like relationships between development and the final size of brain regions, but a description of the conditions in which the various heterochronic parameters (the rates ky and kx, the time variations Δa and Δb) change is still absent.

BL, Darlington RB (1995). Linked regularities in the development and evolution of mammalian brains. Science 268: 1578-1584. S, Collines CE, Wong P, Kaas JH (2007). Cellular scaling rules for primate brains. PNAS 104: 3562-3567. S, Mota B, Lent R (2006). Cellular scaling rules for rodent brains

⁴ Finlay BL, Darlington RB, Nicastro N (2001). Developmental structure in brain evolution. Behavioral and Brain Sciences 24: 263-308.

⁵ Alberch P, Gould SJ, Oster GF, Wake DB (1979). Size and shape in ontogeny and phylogeny. Paleobiology 5: 296-317.